A surgical sealant (hereinafter referred to as “sealant”) is a material that is applied after suturation of an affected part in a biological tissue (hereinafter referred to as “tissue”) such as blood vessel and skin and forms a membrane to thereby prevent emigration of blood and body fluid, oozing, leakage of gas, and the like. The scope of surgical applications includes respiratory surgery, digestive system surgery, cardiovascular surgery, oral cavity surgery and the like. For a surgical sealant, (1) excellent application property, (2) high strength of a gel membrane formed from the sealant, and (3) a short gelation time, are required. Furthermore, it is preferable that (4) the gel membrane has high interfacial adhesion strength against a tissue, and (5) the gel membrane provides small change in water content and is excellent in flexibility.
Currently, sealants that are mainly used are fibrin-based surgical sealants, and Bolheal (trade name, manufactured by Kaketsuken) is exemplified as a product. This surgical sealant is constituted by a component derived from a biological body, and thus has high biocompatibility, but has a problem that it has low adhesion strength.
It has been clarified in recent years that a surgical sealant including human serum albumin (Human Serum Albumin: hereinafter HSA) and a crosslinker has high adhesion strength (Non-patent Literature 1). HSA is a blood serum protein made from a blood product, and is a globular, negatively-charged acidic protein having a molecular weight of 69,000 and a diameter of about 10 nm. Furthermore, as the crosslinker, tartaric acid (Disuccinimidyl Tartarate: hereinafter DST) is used. However, when a blood product is used, the surgical sealant is classified into a medicament, and thus requires much labor in view of acceptation and approval. Furthermore, in the case when the surgical sealant is deemed as a medicament, the history of use thereof should be continuously kept for 20 years after the approval, and thus there is a problem that much labor is required.
Therefore, use of a gelatin, which is a non-blood product, instead of HSA, has been considered. For example, Patent Literature 1 discloses a medical material prepared by crosslinking a gelatin with poly(L-glutamic acid) derivative with succinimdyl groups. Furthermore, Patent Literature 2 relates to a tissue adhesion film, and discloses a tissue adhesion film made from a gelatin or a collagen. However, these materials have a problem that their sealing strength, for which both membrane strength and interfacial adhesion strength are required, are insufficient. Furthermore, Patent Literature 3 relates to a tissue adhesion constitution, and discloses a tissue adhesion constitution in which a particulate synthesis and/or crosslinkable material and a particulate material are mixed. However, this tissue adhesion constitution also has a problem that it has insufficient sealing strength.
In order to solve the above-mentioned problems, the present inventors have synthesized a gelatin having hydrophobic groups at the side chains by using a method for derivatizing a gelatin (Non-patent Literature 1), and suggested a tissue adhesive including said gelatin and a crosslinker (Patent Literature 4).